Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60% of these infections are associated with an implanted medical device causing >$4.5 billion medical costs in 1992 and ~80,000 deaths annually. It is estimated that over 5 million artificial or prosthetic parts are implanted per annum in the U.S. alone. Our goal, with NIH support, is to engineer biomaterials that will solicit a short- and long-term immune response to specific bacterial colonization. For short-term immediate defense, model biomaterials will release fusion protein complexes - artificial opsonins - designed to enhance the coupling of invading bacteria to monocyte/macrophage (MO); thus promoting phagocytosis. For long-term protection, the biomaterial will transfect antigen-presenting cells (specifically dendritic cells - DCs) to produce T- and B-cell memory and antibody expression, and potentially stimulate direct native killer T-cell responses. PUBLIC HEALTH RELEVANCE: It is estimated that over 5 million artificial or prosthetic devices are implanted per annum in the U.S. alone. However, 70% of hospital-acquired infections are associated with implants or indwelling medical devices, with the case-to-fatality ratio between 5-50%. In this 5-yr NIH RO1 research grant, we will develop a novel class of biomaterials that promote healing while preventing bacterial colonization and subsequent infections.